Study of Novel Types 1 and 3 Oral Poliomyelitis Vaccines

NCT ID: NCT04529538

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 226 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-26
• Study Completion Date: 2023-02-17

Brief Summary

The purpose of this study is to assess the safety (primary objective), the ability to trigger the production of antibodies (immunogenicity; a secondary objective) and presence of vaccine virus in the stool (fecal shedding; a secondary objective) of two novel oral polio vaccines (nOPV), novel oral poliomyelitis vaccine type 1 (nOPV1) and novel oral poliomyelitis vaccine type 3 (nOPV3), as compared to Sabin strain monovalent oral poliomyelitis vaccine (mOPV) controls, in healthy adults.

Detailed Description

This multicenter trial is the first-in-human assessment of two novel oral polio vaccines for poliovirus type 1 and type 3. It will be a 4-cohort, 8-arm, randomized, observer-blind, controlled trial, with Sabin monovalent vaccines serving as the control for each type:

Cohort 1: Healthy adults with an exclusive inactivated poliovirus vaccine (IPV) prior vaccination history will be randomized in a 1:1 ratio and allocated to receive nOPV1 (Group 1) or mOPV1 (Group 2).

Cohort 2: Healthy adults with an OPV-containing prior vaccination history will be randomized in a 2:1 ratio and allocated to receive two doses of nOPV1 (Group 3) or mOPV1 (Group 4), respectively;

Cohort 3: Healthy adults with an exclusive IPV prior vaccination history will be randomized in a 1:1 ratio and allocated to receive nOPV3 (Group 5) or mOPV3 (Group 6);

Cohort 4: Healthy adults with an OPV-containing prior vaccination history will be randomized in a 2:1 ratio to study groups 3 and 4 and allocated to receive two doses of nOPV3 (Group 7) or mOPV3 (Group 8), respectively.

Conditions

Poliomyelitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Group1: nOPV1 (IPV History)

Healthy adults fully vaccinated against polio exclusively by IPV were administered 1 vaccination of novel OPV type 1 (nOPV1) containing 10\^6.5 cell culture infectious dose 50% (CCID50) on Day 1.

Group Type: EXPERIMENTAL

Novel Oral Polio Vaccine Type 1 (nOPV1)

Intervention Type: BIOLOGICAL

Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

Group 2: mOPV1 (IPV History)

Healthy adults fully vaccinated against polio exclusively by IPV were administered 1 vaccination of mOPV1 containing 10\^6.0 CCID50 on Day 1.

Group Type: ACTIVE_COMPARATOR

Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)

Intervention Type: BIOLOGICAL

The Sabin mOPV1 control vaccine contains ≥ 10\^6.0 CCID50 per 0.1 mL (2 drops) dose.

Group 3: nOPV1 (OPV History)

Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 vaccinations of nOPV1 containing 10\^6.5 CCID50/dose, given 28 days apart.

Group Type: EXPERIMENTAL

Novel Oral Polio Vaccine Type 1 (nOPV1)

Intervention Type: BIOLOGICAL

Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

Group 4: mOPV1 (OPV History)

Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 doses of mOPV1 containing ≥ 10\^6.0 CCID50/dose, given 28 days apart.

Group Type: ACTIVE_COMPARATOR

Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)

Intervention Type: BIOLOGICAL

The Sabin mOPV1 control vaccine contains ≥ 10\^6.0 CCID50 per 0.1 mL (2 drops) dose.

Group 5: nOPV3 (IPV History)

Healthy adults fully vaccinated against polio exclusively by IPV were administered 1 vaccination of nOPV3 containing 10\^6.5 CCID50 on Day 1.

Group Type: EXPERIMENTAL

Novel Oral Polio Vaccine Type 3 (nOPV3)

Intervention Type: BIOLOGICAL

Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

Group 6: mOPV3 (IPV History)

Healthy adults fully vaccinated against polio by exclusively IPV were administered 1 vaccination of mOPV3 containing ≥ 10\^5.8 CCID50 on Day 1.

Group Type: ACTIVE_COMPARATOR

Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)

Intervention Type: BIOLOGICAL

the Sabin mOPV3 control vaccine contains ≥ 10\^5.8 CCID50 per 0.1 mL (2 drops) dose.

Group 7: nOPV3 (OPV History)

Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 vaccinations of nOPV3 in a dose of 10\^6.5 CCID50/dose, given 28 days apart.

Group Type: EXPERIMENTAL

Novel Oral Polio Vaccine Type 3 (nOPV3)

Intervention Type: BIOLOGICAL

Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

Group 8: mOPV3 (OPV History)

Healthy adults fully vaccinated against polio with an OPV-containing vaccine history were administered 2 vaccinations of mOPV3 containing ≥ 10\^5.8 CCID50/dose, given 28 days apart.

Group Type: ACTIVE_COMPARATOR

Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)

Intervention Type: BIOLOGICAL

the Sabin mOPV3 control vaccine contains ≥ 10\^5.8 CCID50 per 0.1 mL (2 drops) dose.

Interventions

Novel Oral Polio Vaccine Type 1 (nOPV1)

Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

Intervention Type: BIOLOGICAL

Novel Oral Polio Vaccine Type 3 (nOPV3)

Each 0.1 mL (2 drops) dose of vaccine contains approximately 10\^6.5 CCID50.

Intervention Type: BIOLOGICAL

Sabin Monovalent Oral Polio Vaccine Type 1 (mOPV1)

The Sabin mOPV1 control vaccine contains ≥ 10\^6.0 CCID50 per 0.1 mL (2 drops) dose.

Intervention Type: BIOLOGICAL

Sabin Monovalent Oral Polio Vaccine Type 3 (mOPV3)

the Sabin mOPV3 control vaccine contains ≥ 10\^5.8 CCID50 per 0.1 mL (2 drops) dose.

Intervention Type: BIOLOGICAL

Other Intervention Names

Sabin monovalent oral polio vaccine type 3

Eligibility Criteria

Inclusion Criteria

1. Males or females, from 18 to 45 years of age (inclusive) at the time of enrollment

2. Healthy, as defined by the absence of any clinically significant medical conditions, either acute or chronic, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator

3. Willing and able to provide written informed consent prior to performance of any study-specific procedure

4. If female and of childbearing potential*, be not breastfeeding and not pregnant (based on a negative serum pregnancy test at screening and a negative urine pregnancy test during the 24 hours prior to any study vaccination), agreeing to have repeated pregnancy tests prior to any study vaccination, and having practiced adequate contraception** for 30 days prior to first study vaccination and willing to continue using adequate contraception consistently for at least 90 days after the last study vaccination and until cessation of vaccine virus shedding is confirmed

• Females can be considered not of childbearing potential if they are with current bilateral tubal ligation, occlusion or removal, or post-total hysterectomy, or post-bilateral ovariectomy

** Adequate contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label, for example:

• Abstinence from penile-vaginal intercourse
• Combined estrogen and progesterone oral contraceptives
• Hormonal (e.g., progestogen) injections
• Hormonal (e.g., etonogestrel or levonorgestrel) implants
• Contraceptive vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device
• Intrauterine hormonal system
• Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository), and/or progesterone alone oral contraceptive
• Monogamous relationship with vasectomized (≥ 180 days prior to enrollment) partner

5. Resides in study area and is able and willing to adhere to all study restrictions and to all study visits and procedures (as evidenced by a signed informed consent form [ICF] and assessment by the investigator)

6. Agrees not to and has no plans to travel outside the United States (US) until confirmation of cessation of vaccine virus shedding in stool at or after the study Day 57 stool collection

7. Able and willing to be contacted by telephone or text, and willing for study staff to leave telephone voice or electronic messages as needed

8. Neutralizing antibody titer ≥ 1:8 for poliovirus type 1 (for participants in cohorts 1 and 2) and ≥ 1:8 for poliovirus type 3 (for participants in cohorts 3 and 4)

9. For Cohorts 1 and 3 only: previously received at least 3 doses of IPV and with no history of receipt of OPV. For Cohorts 2 and 4 only: previously received a primary polio immunization series containing OPV

Exclusion Criteria

1. Have any condition (medical, psychiatric or behavioral) that, in the opinion of the investigator, would increase the participant's health risks in study participation or would increase the risk of not achieving the study's objectives (e.g., would compromise adherence to protocol requirements or interfere with planned safety and immunogenicity assessments)

2. Receipt of polio vaccine within 12 months before the start of the study

3. Having Crohn's disease or ulcerative colitis or having had major surgery of the gastrointestinal tract involving significant loss or resection of the bowel

4. A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)

5. Any confirmed or suspected immunosuppressive or immunodeficiency condition (human immunodeficiency virus [HIV] infection, or total serum immunoglobulin A (IgA) or immunoglobulin G (IgG) level below the testing laboratory's lower limit of normal [LLN])

6. Administration of any long-acting immune-modifying drugs (e.g., infliximab or rituximab) or the chronic administration (i.e., longer than 14 days) of immunosuppressant drugs (e.g., oral or systemic steroids) or other immune-modifying drugs within 6 months prior to the first vaccine dose or planned use during the study (inhaled and topical steroids are allowed whereas intraarticular and epidural injection/administration of steroids are not allowed)

7. Will have household direct or close professional contact during the study with individuals expected to be immunosuppressed (due to underlying condition or treatments) or individuals who have not yet completed their primary infant polio immunization series (i.e., three doses)

8. Will have household direct or close professional contact during the study with pregnant women

9. Will have household direct or close professional (e.g., neonatal nurses) contact during the study with children less than 2 years of age or with individuals who are encopretic (i.e., infants/toddlers who are not yet toilet trained or other individuals, including adults, with fecal incontinence)

10. Will have professional handling of food, catering, or food production activities during the study

11. Reside in homes with septic tanks

12. Acute illness or fever (body temperature measured orally ≥ 38°C or 100.4°F) at the time of study vaccine administration (once acute illness/fever is resolved, if appropriate, as per investigator assessment, participant may complete screening)

13. Indications of drug abuse or excessive use of alcohol as deemed by the investigator to confound safety assessments or render the participant unable or unlikely to adhere to protocol requirements or provide accurate safety reports

14. Participation in another investigational product (drug or vaccine) clinical trial within 30 days prior to entry in this study or receipt of any such investigational product other than the study vaccine within 30 days prior to the first administration of study vaccine, or planned use during the study period

15. Administration of any vaccine (except seasonal inactivated influenza and COVID-19 vaccines which are prohibited for only 14 days prior to or following each study vaccination) other than the study vaccine or any intramuscular injection within 30 days prior to the first dose of study vaccine or planned administration within 30 days prior to or after any study vaccination.

16. Receipt of transfusion of any blood product or application of immunoglobulins within the 12 weeks prior to the first administration of study vaccine or planned use during the study period

17. Hepatitis B or C virus infection

18. Any hematological# or chemistry** parameter that is out of range of normal†† and is considered clinically significant by the investigator

#Complete blood count (CBC), includes hemoglobin, hematocrit, white blood cell (WBC) count, neutrophil count, lymphocyte count, eosinophil count, and platelet count

**Creatinine, alanine transaminase (ALT), total bilirubin

††Per the site clinical laboratory's reference ranges. All tests with out of range results that are regarded as clinically significant by the clinician must be repeated and determined to be not clinically significant before any participant can be enrolled.

19. The following hematological or chemistry laboratory results will be considered exclusionary, irrespective of assessment of clinical significance:

• Hemoglobin (Male) < 12.5 g/dL
• Hemoglobin (Female) < 11.0 g/dL
• Neutrophil count < 1,000 cells/mm^3
• Eosinophil count > 650 cells/mm^3
• Platelet count < 125,000 cells/mm^3
• Creatinine > 1.4 mg/dL
• ALT > 1.1 X upper limit of normal (ULN) (per the site clinical laboratory's reference ranges)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Viroclinics Biosciences B.V.

INDUSTRY

Sponsor Role: collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jessica Crothers, MD

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Arlene Sena, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Peter Wright, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Mohamed Al-Ibrahim, MB CHB, FACP

Role: PRINCIPAL_INVESTIGATOR

Pharmaron CPC, Inc.

Locations

Pharmaron CPC, Inc.

Baltimore, Maryland, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

University of North Carolina Institute for Global Health and Infectious Diseases (IGHID)

Chapel Hill, North Carolina, United States

University of Vermont Vaccine Testing Center

Burlington, Vermont, United States

Countries

United States

References

Mercer LD, Sena AC, Colgate ER, Crothers JW, Wright PF, Al-Ibrahim M, Tritama E, Vincent A, Mainou BA, Zhang Y, Konopka-Anstadt J, Bandyopadhyay AS, Fix A, Konz JO, Gast C. Safety and immunogenicity of novel live attenuated type 1 and type 3 oral poliomyelitis vaccines in healthy adults in the USA: a first-in-human, observer-masked, multicentre, phase 1 randomised controlled trial. Lancet Infect Dis. 2025 Aug 13:S1473-3099(25)00285-3. doi: 10.1016/S1473-3099(25)00285-3. Online ahead of print.

Reference Type: DERIVED

PMID: 40818478 (View on PubMed)

Thompson KM, Kalkowska DA, Kidd SE, Burns CC, Badizadegan K. Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization. Vaccine. 2024 Feb 6;42(4):819-827. doi: 10.1016/j.vaccine.2023.12.081. Epub 2024 Jan 12.

Reference Type: DERIVED

PMID: 38218668 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CVIA 076

Identifier Type: -

Identifier Source: org_study_id